Genetic circuit supresses appetite in response to blood-fat levels

Genetically modified cells implanted in the body monitor the blood-fat level and produce a satiety hormone if it is too high (Image: Martin Fussenegger / ETH Zurich / Jackson Lab)

Most who have tried it would agree that dieting is a generally unpleasant, and an oftentimes ineffective way to lose weight in the long-term. The biggest hurdle for many is the constant hunger that comes from a change in their regular diet. Biotechnologists at ETH-Zurich have created a genetic helper that could one day put an end to the hunger pangs.

Unlike invasive tummy-tying approaches, such as laparoscopic adjustable gastric bands or stomach stapling, the new genetic slimming aid developed at ETH-Zurich can be implanted in a capsule. The capsule contains human cells that have been implanted with a complex regulatory circuit that was created by combining different human genes that produce proteins and reaction steps.

When released, the synthetic genetic circuit constantly monitors the levels of fat circulating in the blood and, when excessively high fat levels are detected, it produces a hormone that makes the body feel satiated, thus suppressing appetite. The researchers say the circuit can measure several types of fat, including several saturated and unsaturated animal and vegetable fats that are ingested at once.

The research group, headed by ETH-Zurich professor Martin Fussenegger, tested the genetic regulatory circuit on obese mice that had been fed a diet of fatty food. Capsules containing the circuit were implanted in the mice, which then stopped eating excessively and started to lose bodyweight. After their blood-fat levels returned to normal, the circuit stopped producing the satiety-signaling substance.

“The mice lost weight although we kept giving them as much high-calorie food as they could eat,” says Fussenegger, who added that mice fed a diet of normal animal feed with a five-percent fat content didn't reduce their food intake or lose weight.

Although the research team days it will take years to transfer this approach into humans, Fussenegger thinks the implantation of such a gene network could one day provide an alternative to surgical techniques such as liposuction or gastric bands for obese people.